Many viruses form infectious virus particles by budding through the plasma membrane of an infected cell. The interactions and driving forces behind this final assembly are largely unknown. In most budding viruses, a particular viral protein is thought to orchestrate this process. The paramyxoviral matrix (M) protein performs such a role. In this study, the M protein of the model paramyxovirus, Newcastle disease virus, will be examined on three levels to develop a picture of its role in the infected cell. 1) The precise point of the mutations in the M protein in the temperature-sensitive group D mutants and their revertants will be located by sequence analysis of their M protein mRNA's. These mutations may genetically define a region(s) on the M protein which interacts with the transmembranal fusion glycoprotein. 2) The antigenic structure of the M protein will be defined by monoclonal antibodies (MAbs) and the binding sites located on the physical map of M protein. These MAbs will be used to probe the functional regions of the M protein. 3) The associations/functions of the M protein will be examined by developing cell-free association systems. These systems will be tested for specificity, for the effects of mutations on these associations, and to locate the interactive regions on the physical map of M protein. With a better understanding of the M protein and, therefore, the budding process, therapies might be designed to control these virus infections. Such a therapy would be particularly important for diseases such as bronchiolitis or pneumonia in infants, caused by another paramyxovirus, respiratory syncytial (RS) virus. No safe, effective vaccine has been developed for RS virus, despite intensive efforts. Even if such a vaccine is developed, it may not be efficacious during the period of greatest risk, the first six months of life. A better understanding of paramyxovirus budding might provide clues to alternative treatments to decrease virus dissemination.